Caffeine-dependent changes of sleep-wake regulation: Evidence for adaptation after repeated intake

Abstract

Background: Circadian and sleep-homeostatic mechanisms regulate timing and quality of wakefulness. To enhance wakefulness, daily consumption of caffeine in the morning and afternoon is highly common. However, the effects of such a regular intake pattern on circadian sleep-wake regulation are unknown. Thus, we investigated if daily daytime caffeine intake and caffeine withdrawal affect circadian rhythms and wake-promotion in habitual consumers.Methods: Twenty male young volunteers participated in a randomised, double-blind, withinsubject study with three conditions: i) caffeine (150 mg 3 x daily for 10 days), ii) placebo (3 x daily for 10 days) and iii) withdrawal (150 mg caffeine 3 x daily for eight days, followed by a switch to placebo for two days). Starting on day nine of treatment, salivary melatonin and cortisol, evening nap sleep as well as sleepiness and vigilance performance throughout day and night were quantified during 43 h in an in-laboratory, light and posture-controlled protocol.Results: Neither the time course of melatonin (i.e. onset, amplitude or area under the curve) nor the time course of cortisol was significantly affected by caffeine or withdrawal. During withdrawal, however, volunteers reported increased sleepiness, showed more attentional lapses as well as polysomnography-derived markers of elevated sleep propensity in the late evening compared to both placebo and caffeine conditions. Conclusions:The typical pattern of caffeine intake with consumption in both the morning and afternoon hours may not necessarily result in a circadian phase shift in the evening nor lead to clear-cut benefits in alertness. The time-of-day independent effects of caffeine withdrawal on evening nap sleep, sleepiness and performance suggest an adaptation to the substance, presumably in the homeostatic aspect of sleep-wake regulation.

Wide awake at bedtime? The effects of caffeine on sleep and circadian timing in teenagers - a randomized crossover trial

“…In comparison, our participants rated sleepiness in regard to the past minutes and under the acute influence of the drug. Hence, the diverging results can be reconciled within the assumption that caffeine acutely counteracts sleepiness but that this wake-promoting property might vanish if consumed repeatedly or even express as a withdrawal-related higher subjective sleepiness occurring within a certain time after last intake, as has been shown in adults (75,76). Given that one of the main reasons for caffeine intake amongst teenagers is to combat sleepiness and enhance alertness (1), caffeine-induced differences in these variables between acute on-time and habitual daily caffeine intake represents an important target in the future regarding both research and education.…”

Regular caffeine intake attenuates REM sleep promotion and sleep quality in healthy men

“…We employed a double-blind crossover study with three treatments: a caffeine, a withdrawal, and a placebo condition. Random permutations were performed to assign the volunteers to the order of the three conditions, for more details see (Weibel et al, 2020b). As depicted in Fig.…”

“…The following day, saliva was regularly collected in order to quantify the levels of caffeine and its main metabolites. In the evening, we scheduled a one-hour nap (for details see (Weibel et al, 2020b)), which was followed by another wakefulness episode. To minimize masking effects during the in-lab protocol, no time-of-day information was provided, communication was restricted to staff members, light (scheduled wakefulness: < 8 lux; sleep episode: 0 lux), and posture (scheduled wakefulness: semirecumbent; sleep episode: supine) was controlled.…”

“…Regular daytime caffeine intake can lead to adaptations and thus mitigate both caffeine-induced wake-promotion and nighttime sleep-disturbances. Such adaptations are represented in the occurrence of withdrawal symptoms within around 36 h after acute cessation of caffeine, and comprise increased sleepiness (James, 1998;Weibel et al, 2020b), enhanced waking EEG theta activity (Sigmon et al, 2009), and reduced sleep EEG sigma activity (Weibel et al, 2020a). Thus, comparing withdrawal-induced effects on sleep against long-term abstinence and habitual use in the same individuals represents a valid tool to reliably estimate the consequences of daily caffeine intake.…”

“…For this report, we took advantage of an existing data set with exactly these conditions, in which the start of each of the sleep episodes was individually scheduled around the circadian peak of REM sleep promotion. Previous sleep-wake history, light input, posture, meal intake, and circadian phase (estimated by dim-light melatonin onset) were carefully controlled and did not differ between conditions or within individuals (Weibel et al, 2020b). Based on the evidence summarized above, we explored whether the duration and timing of REM sleep change in response to daily daytime caffeine intake (over 10 days) and acute caffeine withdrawal, compared to a long-term (10-day) placebo baseline.…”